Leucine-rich repeat containing G protein-coupled receptor 5 (LGR5, GPR49, FEX) is a receptor for R-spondins that potentiates the canonical Wnt signaling pathway and acts as a stem cell marker of the intestinal epithelium and in hair follicles. Upon binding to R-spondins, such as RSPO1, RSPO2, RSPO3 or RSPO4, it interacts with phosphorylated LRP6 and frizzled receptors and triggers the canonical Wnt signaling pathway to increase expression of target genes. It is involved in the development and maintenance of adult intestinal stem cells during postembryonic development. In immunohistochemistry, it is often used as a marker for LGR5+ multipotent stem cells. It has membranous positivity in various tissues including muscle, the spinal cord, the brain, crypt base columnar cells in the small intestine and in the colon, nascent nephron cell clusters in the developing kidney, populations of cells in the stomach, and the placenta. It is also a useful marker for characterizing stem cells, stem-ness and also poor prognosis in premalignant and cancerous tissues such as glioblastoma, cervical cancer and colorectal carcinoma. References: The UniProt Consortium. Nucleic Acids Res. 47: D506-515 (2019); Nucleic Acids Res. 2016 Jan 4;44(D1):D733-45, PMID:26553804; Gastroenterology. 2010. 138 (5): 1681–96, PMID: 20417836; ScientificWorldJournal. 2008 Nov 23;8:1168-76, PMID: 19030762; Cell Death Dis. 2017 Sep 7;8(9):e3039, PMID: 28880275; Brain Pathol. 2013 Jan;23(1):60-72, PMID: 22805276;